Vaccination is the single most effective mechanism for the control of infectious disease, yet there remain numerous pathogens for which no vaccines exist. For example, the paramyxoviruses include a number of important human pathogens transmitted via the respiratory route such as human respiratory syncytial virus (RSV), the parainfluenza viruses (PIVs), human metapneumovirus, measles virus, and mumps virus (Brown et al. 2007 J. Virol 81:12535; Hall et al. 2009 N. Engl. J. Med. 360:588). The human PIVs (hPIVs) consist of four serotypes (hPIV1-4) and, along with RSV and metapneumovirus, are the most common causes of respiratory tract viral infections in children. The PIVs, RSV, and metapneumovirus are efficiently transmitted by direct contact and exposure to nasopharyngeal secretions (Hall et al. 2009 N. Engl. J. Med. 360:588; Hall et al., 1981 J. Pediatr. 99:100). Nearly all children become infected with RSV by age 1, with hPIV3 by age 2, and with hPIV1 and hPIV2 by age 5 (Schickli et. al. 2009 Hum. Vaccin. 5:582; Graham et al. 2011 Immunol Rev. 239:146). In the United States, RSV can account for up to 20% hospitalizations of young children in an RSV season with annual costs as high as 0.4 billion dollars (Hall et al. 2009 N. Engl. J. Med. 360:588; Schickli et. al. 2009 Hum. Vaccin. 5:582; Graham et al. 2011 Immunol. Rev. 239:146; Shay et al. 2001 J. Infect. Dis. 183:16; Shay et al. 1999 JAMA 282:1440; Paramore et. al. 2010 Pediatr. Pulmonol. 45:578; Hall et al. 2001 N. Engl. J. Med. 344: 1917; Bourgeois et al. 2009 Pediatrics 124: e1072; Boyce et al. 2000 J. Pediatr. 137: 865). For patients with bronchiolitis and pneumonia, RSV has been identified as the etiologic agent in as many as 90% and 50% cases, respectively (Paramore et. al. 2010 Pediatr. Pulmonol. 45:578; Hall et al. 2001 N. Engl. J. Med. 344: 1917). No licensed vaccines exist for any of these human pathogens.
Sendai virus (SeV) comprises an attractive vaccine and vaccine vector. It can act as a Jennerian vaccine for hPIV-1, the leading cause of laryngotracheobronchitis (pediatric croup), based on amino-acid sequence and antigenic similarities between the two viruses (Gorman et al. 1990 Virology 175: 211; Dave et al. 1994 Virology 199:376; Smith et al. 1994 Virology 205: 453). SeV can also be manipulated by reverse genetics to produce recombinant vaccines that could to vaccinate against virtually any other pathogen(s) of choice. The desirability of a Sendai virus-based vector depends on the following: (i) capacity for facile rescue by reverse genetics, (ii) capacity to carry a marker gene for virus tracking in vivo and in vitro, (iii) support of expression and immunogenicity of foreign proteins when respective genes are introduced into different positions within the SeV genome, (iv) limited growth in primates, (v) sufficient replication-competence to support vaccination and immunogenicity in primates. Because the hPIVs and RSV cause most of the respiratory viral disease infections in the most vulnerable population of children, infants, and elderly, novel methods and compositions are needed to protect humans from parainfluenza virus and respiratory syncytial virus infections.